The primary objective of this program is to conduct the necessary physical, biological and clinical studies to evaluate the efficacy, potential benefit and role of negative pi mesons (pions) in management of all types and stages of solid tumors not well managed by current methods or combinations thereof. The University of New Mexico Cancer Research and Treatment Center and the Los Alamos Scientific Laboratory have been engaged since 1972 in a joint research effort to test the radiotherapeutic potential of pions produced by the 800 MeV proton linear accelerator at Los Alamos. This accelerator is the only one in the world presently capable of producing pions at sufficient intensity for medical testing, and institutions throughout the nation are sending appropriate patients to this facility for pion radiotherapy. These studies have been conducted in the past under two grants (CA-14052 for preclinical studies and CA-16127 for clinical studies); the two grants are being combined in this application. Randomized Phase III clinical trials of pion radiotherapy for 13 anatomic sites are expected to be activated by the start of the three-year period proposed in this application. Progress to date in the clinical, biological, and physical studies, as well as research plans for the proposed three-year period are described in the text of this application for each of the four components: clinical investigations, biology, physics, and core.